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Lamotrigine and Bupropion for Meniere's Disease

Phase 2
Recruiting
Conditions
Meniere Disease
Ménière's Vertigo
Vertigo, Intermittent
Vertigo, Aural
Interventions
Registration Number
NCT05420350
Lead Sponsor
Dent Neuroscience Research Center
Brief Summary

This is a double-blind, placebo-controlled clinical trial to assess whether treatment with lamotrigine and bupropion is more effective than placebo to reduce definitive Meniere's vertigo attacks (DMVA) and dizziness in patients with Meniere's disease. Thirty four participants will be randomized to treatment or placebo groups. Each participant will take part in the trial for 34 weeks, or approximately 9 months.

Detailed Description

Participants begin with a 4 week lead-in after screening to determine the frequency and severity of vertigo they are experiencing. Participants continue to track their vertigo episodes throughout the study. At Visit 2, if eligible, participants begin the titration of lamotrigine or matching placebo. Participants are on the full dose of lamotrigine/placebo for 8 weeks, and then begin taking bupropion or matching placebo along with lamotrigine or matching placebo for 12 weeks. At Week 27, participants are tapered off lamotrigine/placebo and stop taking bupropion/placebo. Participants have an in-person visit approximately once a month over 9 months.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
34
Inclusion Criteria
  • Adult participants, male and female aged 18 years or older
  • Diagnosis of definitive unilateral Meniere's disease according to the AAO-HNS 1995 criteria, confirmed by an ENT or qualified medical professional
  • Be experiencing active vertigo
  • Be in good general health as evidenced by medical history or, otherwise, have all other co-existing medical or psychiatric conditions stable, and or no greater than moderate in severity, as determined by the PI
  • Females of childbearing potential must use at least two forms of acceptable contraception, or remain abstinent; male participants must be willing to use condoms or other methods to ensure effective contraception with a partner
  • Be willing to comply with all study procedures and availability for the duration of the study
  • Be able to provide informed written consent, including agreement to privacy language either within the informed consent or in ancillary documents compliant with Health Insurance Portability and Accountability Act (HIPAA) before the initiation of any study-related procedures
Exclusion Criteria
  • A diagnosis of bilateral Meniere's disease according to the AAO-HNS 1995 criteria, confirmed by an ENT or qualified medical professional
  • Be pregnant or lactating
  • Have active migraine-associated vertigo
  • Not be able to accurately identify and report episodes of vertigo
  • Diagnosis of any other neuro-otologic disease or major vestibular abnormality found during screening that could confound the evaluation of Meniere's symptoms
  • Have a history of intolerance or sensitivity to lamotrigine
  • Previously failed the study drug
  • Received an intratympanic gentamicin injection(s) or endolymphatic sac surgery within in the last year
  • Have a family history of unexplained deafness
  • Have any current diseases or conditions that may be associated with an altered perception of processing stimuli
  • Have a history of substance abuse within the preceding 6 months prior to screening
  • Have non-vertiginous dizziness (orthostatic or panic disorder) unless it could be clearly differentiated from Meniere's attacks by the participant

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboThe placebo will match the lamotrigine and bupropion dosage, frequency, and duration.
Lamotrigine and BupropionLamotrigine and BupropionLamotrigine will be taken orally for a duration of 28 weeks, consisting of a six-week titration, 20-week study period, and two-week taper. Possible doses are 25mg one a day, 50mg once a day, 50mg twice a day, 75mg twice a day during titration; 125mg twice a day for the study period; and 125mg once a day during the two-week taper. Patients who discontinue at any point of the study will have a two-week taper of lamotrigine. Bupropion will be taken orally for the duration of 20 week at the dosage of 100mg twice a day.
Primary Outcome Measures
NameTimeMethod
Change in Ménière's vertigo attack frequency between groupsDuration of lead-in to completion at week 30

Number of Definitive Ménière's Vertigo attacks (DMVA), Number of Dizziness Days and overall dizziness severity during each 4-week of titration, and treatment compared to the 4-week lead-in phase. Vertigo ratings will be collected on a daily symptom diary throughout the study. DMVA is defined as vertigo for more than 20 minutes and corresponds to a vertigo rating of 3 or 4 on the daily symptom diary. A Dizziness Day is defined as vertigo rating of 1, 2, 3 or 4 on the daily symptom diary. Dizziness severity is the sum of all ratings (0-4) during each 4-week period.

Change in Ménière's vertigo attack frequency lamotrigine alone compared to lamotrigine and bupropionWeek 1 to Week 27

Number of Definitive Ménière's Vertigo attacks (DMVA), Number of Dizziness Days and overall dizziness severity during each 4-week of treatment of lamotrigine alone and treatment of bupropion and lamotrigine.Vertigo ratings will be collected on a daily symptom diary throughout the study. DMVA is defined as vertigo for more than 20 minutes and corresponds to a vertigo rating of 3 or 4 on the daily symptom diary. A Dizziness Day is defined as vertigo rating of 1, 2, 3 or 4 on the daily symptom diary. Dizziness severity is the sum of all ratings (0-4) during each 4-week period.

Secondary Outcome Measures
NameTimeMethod
Changes in patients' self-assessment of anxietyBaseline (Week 1) and Visit 8 (Week 27)

Between groups comparisons of General Anxiety Disorder-7 (GAD-7) at Week 27 compared to the baseline visit at the end of the lead-in phase. GAD-7 at baseline compared to evaluation at end of treatment.

Scores range from 0-21 with higher numbers meaning more severe anxiety.

Changes in patients' self-assessment of dizzinessBaseline (Week 1) and Visit 8 (Week 27)

Between groups comparisons of Dizziness Handicap Inventory (DHI) at Week 27 compared to the baseline visit at the end of the lead-in phase. DHI at baseline compared to evaluation at end of treatment.

Scores range from 0-100 with higher scores meaning more severe dizziness handicap

Changes in patients' self-assessment of overall affect of symptomsBaseline (Week 1) and Visit 8 (Week 27)

Between groups comparisons of Ménière's Disease Patient-Oriented Symptom-Severity Index (MDPOSI) at Week 27 compared to the baseline visit at the end of the lead-in phase. MDPOSI at baseline compared to evaluation at end of treatment.

Scores range from 0-80 with higher numbers indicating more frequent and severe symptoms.

Changes in patients' self-assessment of symptom impact on daily life functionBaseline (Week 1) and Visit 8 (Week 27)

Between groups comparisons of Ménière's Disease Self-Assessment (MDSA) at Week 27 compared to the baseline visit at the end of the lead-in phase. MDSA at baseline compared to evaluation at end of treatment.

Scores range from 1-6 with higher numbers representing Ménière's Disease symptoms having a greater affect on the patient's ability to function in daily life.

Changes in patients' self-assessment of depressionBaseline (Week 1) and Visit 8 (Week 27)

Between groups comparisons of Patient Health Questionnaire-9 (PHQ-9) at Week 27 compared to the baseline visit at the end of the lead-in phase. PHQ-9 at baseline compared to evaluation at end of treatment.

Scores range from 0-27 with higher numbers meaning more severe depression.

Trial Locations

Locations (1)

Dent Neurologic Institute

🇺🇸

Amherst, New York, United States

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